1. Validation of 99mTc-labeled '4+1' fatty acids for myocardial metabolism and flow imaging
- Author
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Gerd Wunderlich, Martin Walther, Peter Dieterich, Jens Pietzsch, Hans-Jürgen Pietzsch, Ralf Bergmann, Johannes Weichsel, Peter Mirtschink, Joachim Kropp, Sebastian Stehr, Annette Pexa, Bert Binas, and Andreas Deussen
- Subjects
Cancer Research ,Biodistribution ,Very low-density lipoprotein ,medicine.medical_specialty ,CD36 ,Fatty acid-binding protein ,chemistry.chemical_compound ,Myocardial perfusion imaging ,Internal medicine ,medicine ,Percent Injected Dose ,Radiology, Nuclear Medicine and imaging ,Inner mitochondrial membrane ,medicine.diagnostic_test ,biology ,Chemistry ,Albumin ,Metabolism ,Cytosol ,Endocrinology ,Biochemistry ,Mitochondrial matrix ,Microsome ,biology.protein ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Etomoxir ,Lipoprotein - Abstract
Introduction Our group has synthesized technetium-labeled fatty acids (FA) that are extracted into the myocardium and sequestered due to heart-type fatty acid binding protein (H-FABP) binding. In this article, we further address the detailed subcellular distribution and potential myocardial metabolism of [ 99m Tc]"4+1" FA. Methods Experiments were conducted using isolated hearts of Wistar rats, as well as of wild-type and H-FABP −/− mice. Myocardium samples underwent subcellular fractionation [subsarcolemmal mitochondria (SM), intermyofibrillar mitochondria (IM), cytosol with microsomes, and nuclei and crude membranes] and analysis by thin-layer chromatography and high-performance liquid chromatography. Results The largest fraction of tissue radioactivity was associated with cytosol [79.69±8.88% of infused dose]. About 9.07±0.95% and 3.43±1.38% of the infused dose were associated with SM and IM fractions, respectively. In the rat heart, etomoxir, an inhibitor of carnitin-palmitoyl transferase I, did not significantly decrease radioactivity associated with mitochondrial fractions, whereas myocardial extraction of [ 123 I]-labeled 15-( p -iodophenyl)-pentadecanoic acid (13.26% vs. 49.49% in controls) and the radioactivity associated with the SM and IM fractions were blunted. The percentage of the infused dose in the mitochondrial and crude fractions increased with the number of NH-amide groups of the FA derivative. Absence of H-FABP significantly decreased radioactivity count in the cytosolic fraction ( P 99m Tc]"4+1" FA could be detected in any isolated heart. Conclusions Myocardial [ 99m Tc]"4+1" FA extraction reflects binding to H-FABP and membrane structures (including the mitochondrial membrane). However, the compounds do not undergo mitochondrial metabolism because they do not reach the mitochondrial matrix.
- Published
- 2009